[Calcitonin].

Abstract

Calcitonin is a potent inhibitor of osteoclastic bone resorption and has been widely used for the treatment of osteoporosis. Nasal calcitonin, instead of injectable form, is more popular in Europe and United States, while only injectable form has been approved in Japan. The regimen, dose, frequency is remarkably different from study to study, and the standard regimen has not been established for osteoporosis. Fifty to 100 units of salmon calcitonin has been used daily intramuscularly in Europe. Recent trial using nasal calcitonin has shown the similar effects on the bone as the injectable form although the actual resorptionis not so high. In Japan, once weekly 20 units if eel calcitonin analogue injection has been approved for osteoporosis. After administration in the form of either nasal or injectable preparation, peak serum concentration reaches more than 100 pg/ml, far exceeding 10(-11) M, at which level osteoclast bone resorption is rapidly impaired with disappearance of actin ring formation. It is reflected by the decrease of urinary pyridinoline cross-links excretion. Consecutive treatment with calcitonin reduces the calcitonin receptors on the surface of osteoclasts as well as osteoclast precursors, while they are still TRAP positive, suggesting that they retain bone resorbing activity. That may be one of the mechanisms of escape phenomenon. We are not sure whether daily administration of calcitonin can avoid the escape phenomenon and can maintain the bone volume. The standard preparation should be determined by the longer clinical trials with new bone markers and bone mass measurement as the endpoints.